珊瑚状遗传性先天性白内障一家系致病基因的连锁分析及候选基因研究  

Gene mapping and analysis of candidate genes in a Chinese family with autosomal dominant congenital coralliform cataract

作　　者：鞠宏[1] 赵堪兴[1] 王犁明[1] 王玉川[1] 应铭[1] 高翔 

机构地区：[1]天津医科大学眼科临床学院天津市眼科医院天津市眼科研究所天津市眼科学与视觉科学重点实验室,300020 [2]河南省焦作卫生学校

出　　处：《中华眼科杂志》2012年第8期713-717,共5页Chinese Journal of Ophthalmology

摘　　要：目的明确一个具有常染色体显性遗传特点的珊瑚状先天性白内障家系中致病基因及其突变的类型。方法系列病例研究。对珊瑚状遗传性先天性白内障一家系共18名成员进行详细的临床检查，确定其临床表型。提取9位家系成员（4名患者，均为男性，3名正常同胞，2名配偶，年龄4—79岁）的外周血DNA，利用连锁分析进行排除定位，确定候选基因。对连锁区域内的候选基因进行基因序列分析。结果连锁分析结果显示在D2S325得到最高LOD值为1．51，在D11S925得到LOD值为1．20，支持其与该家系先天性白内障疾病相关候选基因有连锁关系；CRYGD、CRYGC、CRYAB基因可能为该家系先天性白内障疾病相关候选基因。测序结果显示该家系患者CRYGD基因第二外显子第70位碱基由C突变为A，导致第23位的脯氨酸变成了苏氨酸（P23T），且这一错义突变与疾病表型完全共分离。CRYGC基因、CRYAB基因编码区未发现突变。结论珊瑚状遗传性先天性向内障一家系的致病原因是CRYGD基因，第二外显子第70位碱基由C突变为A。Objective To map and to identify the causal gene of autosomal dominant congenital coralliform cataract （ADCC） in a Chinese family. Methods Case series study. Clinical features of all affected members in this family were examined. Blood samples were collected from nine family members for genetic linkage analysis. Polymorphic microsatellite markers were selected from the regions which harbor all known loci linked with ADCC. Direct genomic sequencing was used to evaluate the candidate gene. Results The affected members in this family showed classic phenotype of ADCC. The maximum two-point LOD score of 1.51 was obtained for marker D25325 （0 = 0）. The LOD score of 1.20 was obtained for marker D115925. The CRYGC/CRYGD gene located on 2q33-q35 and the CRYAB gene located on 11q22-q22, 3. Therefore, the CRYGC/CRYGD and CRYAB gene may be the candidate gene in this family. Sequencing of the coding regions of the CRYGD gene showed the presence of a hetcrozygous C-~A transversion at nucleotide 70 in exon 2 of CRYGD that is associated with cataracts in this family. This mutation resulted in a proline to threonine substitution at amino acid 23 of the protein in the first of the four Greek key motifs that characterized this protein. No mutation in all exons of CRYGC and CRYAB gene were found in the family. Conclusion Direct DNA sequence analysis revealed a C-to-A transition at nucleotide 70 of the CRYGD gene in this ADCC family

关 键 词：白内障 眼疾病 遗传j生 连锁(遗传学) 序列分析 DNA γ晶体蛋白质类 

分 类 号：R776.1[医药卫生—眼科]